Clustered regularly interspaced short palindromic repeats (CRISPR)-mediated manipulation of genomic information is becoming more versatile by combining nuclease-deficient CRISPR systems with a wide variety of effectors including base-editing deaminases, transcriptional regulators, and epigenetic modifiers. The programmable binding ability of CRISPR systems is essential when the systems are employed as targeting domains to recruit the effectors to specific genomic loci. The discovery of a variety of Cas9 orthologs and engineered variants enables high-fidelity genome editing and a wider selection of genomic targets, and CRISPR-mediated deaminases enable more precise and predictable genome editing compared with CRISPR nuclease-based editing. Finally, combining transcriptional regulators with CRISPR systems can control expression of specific genes in a genome. Some applications and future challenges of CRISPR-derived tools are also discussed.

通过将核酸酶缺陷型CRISPR系统与多种效应子（包括碱基编辑脱氨酶，转录调节子和表观遗传修饰子）相结合，成簇的规则间隔的短回文重复序列（CRISPR）介导的基因组信息操作变得更加通用。当将CRISPR系统用作靶向结构域以将效应子募集至特定基因组位点时，CRISPR系统的可编程结合能力至关重要。与基于CRISPR核酸酶的编辑相比，发现了多种Cas9直向同源物和工程变体，可实现高保真基因组编辑和更广泛的基因组靶标选择，而CRISPR介导的脱氨酶可实现更精确和可预测的基因组编辑。最后，将转录调节因子与CRISPR系统结合使用可以控制基因组中特定基因的表达。还讨论了CRISPR衍生工具的一些应用和未来的挑战。